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Down syndrome

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Down syndrome
SpecialtyMedical genetics, neurology Edit this on Wikidata
Frequency0.1%

Down syndrome (US, Canada and other countries) or Down's syndrome (UK and other countries) encompasses a number of chromosomal abnormalities, of which trisomy 21 (an aneuploid) is the most common, causing highly variable degrees of learning difficulties as well as physical disabilities. It is named for John Langdon Down, the British doctor who first described it in 1866.

Overview

The incidence of Down syndrome is estimated at 1 per 800 births, making it the most common human aneuploidy. Maternal age influences the chance of conceiving a baby with the syndrome. At age 20 to 24, it is 1/1490, while at age 40 it is 1/106, and at age 49 is 1/11. (Hook EB., 1981). Although the chance increases with maternal age, most children with Down syndrome (80%) are born to women under the age of 35. This reflects the overall fecundity of that age group. Many standard screens of pregnancies indicate Down syndrome, although they are not very accurate. Genetic counseling along with genetic testing, such as amniocentesis or chorionic villus sampling, are usually offered to families who may have an increased chance of having a child with Down syndrome.

While most children with Down syndrome have a lower than average cognitive function, some have earned college degrees with accommodations, and nearly all will learn to read, write and do simple math. The common clinical features of Down syndrome include any of a number of features that also appear in people with a standard set of chromosomes. They include a "simian crease" (a single crease across one or both palms), almond shaped eyes, shorter limbs, heart and/or gastroesophageal defects, speech impairment, and perhaps a higher than average risk of incidence of Hirschsprung's disease. Young children with Down syndrome are also more prone to recurrent ear infections and obstructive sleep apnea.

Early educational intervention, screening for common problems, such as thyroid functioning, medical treatment where indicated, a conducive family environment, vocational training, etc., can improve the overall development of children with Down syndrome. On the one hand, Down syndrome shows that some genetic limitations cannot be overcome; on the other, it shows that education can produce excellent progress whatever the starting point. The commitment of parents, teachers, and therapists to individual children has produced previously unexpected positive results.

History

John Langdon Down first characterized Down syndrome in 1862 (widely published in 1866). Because of his perception that Down syndrome children share physical similarities with Mongolians, he used the terms mongolism or mongolian idiocy. At the time, the vast majority of people with Down syndrome were institutionalized. The reference to racial characeristics was typical of the day and the growing eugenics movement. Into the 20th Century, individuals with Down syndrome (and other disabilities) were institutionalized and often forcibly sterilized (33 of the, then, 48 United States had forced sterilization laws). The German program "Aktion T-4" (1940) was a euthanasia program aimed at various disabilities, including Down syndrome. These programs have since been discredited and forced institutionalization is atypical in Western countries.

In 1959, Professor Jérome Lejeune discovered that Down syndrome is a chromosomal irregularity [1]. The chromosomal irregularity was identified as trisomy 21. The human karyotype is numbered from largest to smallest (excluding the X and Y), and Lejeune ascribed the trisomy to chromosome 21, the second smallest. This is incorrect. The chromosome that causes Down syndrome should have been designated 22, the smallest. By the time the mistake was discovered, it was too late to change the karyotype order.

In 1961 a group of geneticists wrote to the editor of The Lancet suggesting that the name be changed. They gave him several choices, and he chose Down's Syndrome. The World Health Organization (WHO) confirmed this designation in 1965 2. In 1974, the United States National Institute of Health called a conference to standardize the naming of diseases and disorders. They recommended eliminating the possessive form ("The possessive form of an eponym should be discontinued, since the author neither had nor owned the disorder."). Down syndrome is the accepted term in the USA, Canada and other countries, and the possessive form is used in the United Kingdom and other countries.

Genetics

Down syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the 21st chromosome, either in whole (trisomy 21) or part (such as due to translocations). The effects of the extra copy varies greatly from individual to individual, depending on the extent of the extra copy, genetic background, environmental factors, and random chance. Down syndrome can occur in all human populations, and analogous effects have been found in other species, such as chimpanzees and mice.

Down syndrome has four root causes:

  • Trisomy 21 is caused by a meiotic nondisjunction event. In this case the child has three copies of every gene on chromosome 21. This is the cause of 95% of observed Down syndromes.
  • The extra material is due to a Robertsonian translocation. The long arm of 21 is attached to another chromosome (often chromosome 14 or itself). The parent with the translocation is missing information on the short arm of 21, but this does not have apparent effects. Through normal disjunction during meiosis, gametes are produced with extra copies of the long arm of chromosome 21. There is variability in the extra region. This is the cause of 2-3% of the observed Down syndromes, and is often referred to as 'familial Down syndrome'.
  • The individual is a mosaic of normal chromosomal arrangements and trisomy 21. This can occur in one of two ways: A nondisjunction event during an early cell division leads to a fraction of the cells with trisomy 21; or A Down syndrome embryo undergoes nondisjunction and some of the cells in the embryo revert back to the normal chromosomal arrangement. There is considerable variability in the fraction of trisomy 21, both as a whole and tissue-by-tissue. This is the cause of 1-2% of the observed Down syndromes. Is it likely that all people have an extremely small fraction of their cells that are trisomy 21.
  • Rarely, a region of the 21st chromosome will undergo a duplication event. This will lead to extra copies of some, but not nearly all, of the genes on chromosome 21.

Most Down syndrome cases occur spontaneously. There is no known prevention, although some factors, such as increased maternal age, can increase the chance of occurrence. The genetic basis itself cannot be treated, and the variety of expression requires targeting treatment to each individual.

Prenatal Screening

Pregnant women can be screened for various complications in their pregnancy. Some screens are designed to indicate neural tube defects (such as spina bifida), Trisomy 18, or Down syndrome, and other possible problems. There are two common non-invasive screens that can indicate an increased chance for a Down syndrome fetus.

  • Triple Screen. This test measures the maternal serum alpha feto protein (a fetal liver protein), estriol (a pregnancy hormone), and human chorionic gonadotropin (hCG, a pregnancy hormone). This screen is done at the 15th - 20th week. It can detect about 60% of Down syndrome pregnancies. However, it has a 6.5% Initial Positive Rate (IPR) for Down syndrome. Compare this to the 0.1% chance for Down syndrome birth. As with most screens, the chance of a false positive is great. The majority of women with a positive result will not have a Down syndrome birth.
  • AFP/Free Beta Screen. This test measures the alpha feto protein, produced by the fetus, and free beta hCG, produced by the placenta. It can be done somewhat earlier than the triple screen (13th to 22nd week). It has an IPR of 2.8% and a detection rate of about 80%. It is not as common as the triple screen.

Even with the best non-invasive screens, the detection rate is only 80% and the rate of false positive is nearly 3%. False positives can be caused by undetected multiple fetuses, incorrect date of pregnancy, or normal variation in the proteins.

Confirmation of the test is normally accomplished with amniocentesis. This is an invasive procedure and involves taking amniotic fluid from the mother and identifying fetal cells. The risk of spontaneous abortion is approximately 1 in 200 to 1 in 300. The lab work can take a couple of weeks. It will detect over 99.8% of all numerical chromosomal problems, and has a very low false positive rate.

Education

Cognitive development in children with Down syndrome is quite variable. Many can be successful in school, while others struggle. Because of this variability in expression of Down syndrome, it is important to evaluate children individually. The cognitive problems that are found among children with Down syndrome are also found among children without Down syndrome. This means that parents can take advantage of general programs that are offered through the schools or other means. Children with Down syndrome have a wide range of abilities. It is not possible at birth to predict their capabilities. The identification of the best methods of teaching each particular child ideally begins soon after birth, through early intervention programs.

Most children with Down syndrome are in the mild to moderate range of mental retardation. Emotional and social abilities follow a more normal path, moderated by whatever cognitive disability the child may have. Very early social and emotional development show about a one to three month delay on average.

Language skills show a difference between understanding speech and expressing speech. It is common for children with Down syndrome to need speech therapy to help with expressive language. Fine motor skills often lag behind gross motor skills and can interfere with cognitive development. Occupational therapy can address these issues.

Mainstreaming of children with Down syndrome is controversial. Mainstreaming is when students of differing abilities are placed in classes with their chronological peers. Children with Down syndrome do not age emotionally/socially and intellectually at the same rates as children without Down syndrome, so eventually the intellectual and emotional gap between children with and without Down syndrome widens. Complex thinking as required in sciences but also in history, the arts, and other subjects is often beyond their abilities, or achieved much later than in most children. Therefore, if they are to benefit from mainstreaming without feeling inferior most of the time, special adjustments must be made to the curriculum.

Children with Down syndrome can also be placed in classes with cognitive peers. After preschool, the difference in age makes this problematic.

A danger in not mainstreaming is underestimating their abilities. This was more common in institutions, where Down syndrome children often failed to reach their potential despite being capable of much more, but this issue is very real and present in the modern school system as well. Some European countries such as Germany and Denmark advise a two-teacher system, whereby the second teacher takes over a group of disabled children within the class. A popular alternative is cooperation between special education schools and mainstream schools. In cooperation, the core subjects are taught in separate classes, which neither slows down the non-disabled students nor neglects the disabled ones. Social activities, outings, and many sports and arts activities are performed together, as are all breaks and meals.

Alternative treatment

The Institutes for The Achievement of Human Potential (IAHP [2]) is a non-profit organization which treats children who have, as The IAHP terms it, "some form of brain injury," including children with Down syndrome. The IAHP offers a number of intellectual, physical, and physiological programs for children with neurological challenges. The approach of "Psychomotor Patterning" is not proven (see, for example, Psychomotor Patterning), and is considered alternative medicine. (IAHP) has the results of its treatment for over 1700 children on its website. No peer review is claimed.

Health

Individuals with Down syndrome are at risk for various medical conditions. There is no way to predict what conditions they will have, if any. In addition, all these medical conditions can be exhibited by individuals without Down syndrome. It is important to keep these medical risks in mind while undergoing wellness checkups. The following links point to health flowcharts that can help parents with normal checkups 6.

A partial list of risks is given below. Risks run from 80% (hearing deficits) to 50% (congenital heart defects) to 20% (hypothyroidism) to rare but significantly increased risks (Leukemia).

There is some evidence that individuals with Down syndrome have a much lower rate of lung cancer than others.

As with all risks, this does not mean that everyone with Down syndrome will get these diseases, nor that an individual will get any of them. The concentration on wellness in individuals with Down syndrome and increased medical technology has vastly improved the length and quality of life. Current estimates (7) give life expectancy in the United States as 55 years, compared to 77 years for the population in general. This life expectancy is a tremendous increase in recent years.

Medical research

Of the inborn differences that affect intellectual capacity, Down syndrome is the most prevalent and best studied. Down syndrome is a term used to encompass a number of genetic disorders of which trisomy 21 is the most frequent (95% of cases). Discovered by the Parisian physician Jerome Lejeune in 1959, Trisomy 21 is the existence of the third copy of the chromosome 21 in cells throughout the body of the affected person. Other Down syndrome disorders are based on the duplication of the same subset of genes (e.g., various translocations of chromosome 21). Depending on the actual etiology, the degree of impairment may range from mild to severe. In rare cases trisomy 21 is present in some cell lines but not all, due to an anomalous early cell division in the zygote. There is evidence that this variant, called mosaic Down syndrome, may produce less developmental delay, on average, than full trisomy 21. [3] 3

Trisomy 21 results in over-expression of genes located on chromosome 21. One of these is the superoxide dismutase gene. Some (but not all) studies have shown that the activity of the superoxide dismutase enzyme (SOD) is elevated in Down syndrome. SOD converts oxygen radicals to hydrogen peroxide and water. Oxygen radicals produced in cells can be damaging to cellular structures, hence the important role of SOD. However, the hypothesis says that once SOD activity increases disproportionately to enzymes responsible for removal of hydrogen peroxide (e.g., glutathione peroxidase), the cells will suffer from a peroxide damage. Some scientists believe that the treatment of Down syndrome neurons with free radical scavengers can substantially prevent neuronal degeneration. Oxidative damage to neurons results in rapid brain aging similar to that of Alzheimer's disease.

Another chromosome 21 gene that might predispose Down syndrome individuals to develop Alzheimer's pathology is the gene that encodes the precursor of the amyloid protein. Neurofibrillary tangles and amyloid plaques are commonly found in both Down syndrome and Alzheimer's individuals. Layer II of the entorhinal cortex and the subiculum, both critical for memory consolidation, are among the first affected by the damage. A gradual decrease in the number of nerve cells throughout the cortex follows. A few years ago, Johns Hopkins scientists created a genetically engineered mouse called Ts65Dn (segmental trisomy 16 mouse) as an excellent model for studying the Down syndrome. Ts65Dn mouse has genes on chromosomes 16 that are very similar to the human chromosome 21 genes. With this animal model, the exact causes of Down syndrome neurological symptoms may soon be elucidated. Naturally, Ts65Dn research is also likely to highly benefit Alzheimer's research.

While there are a number of commercially promoted dietary supplements on the market, especially in the USA, mainly involving various combinations of vitamins and minerals, none of these have been medically approved for use in the UK for the mass treatment of people with Down syndrome and none appear to lead to any proven lasting benefits. All remain highly controversial.

Challenges

Pregnant women with a diagnosis of Down syndrome

Parents of children with Down syndrome

Individuals with Down syndrome

Down syndrome's sociology

Advocates for people with Down syndrome stress that affected individuals have the same human rights and emotions as any other human beings. Down syndrome is considered grounds for abortion in an increasing number of countries. The number of children born with Down syndrome is decreasing due to the large number of abortions following an early diagnosis of Down syndrome during pregnancy. In a hearing before the German Parliament, doctors stated that 90% of all fetuses prenatally diagnosed with Down syndrome are aborted. This number is consistent with the official statistics, wherein 1500 children with Down syndrome should, statistically, have been born per year (at a prevalence rate of 1:600), but only 63 per annum were listed in the 1995 birth register. In the United States numbers are reported to fluctuate between 70-80% of all women diagnosed during pregnancy will opt to terminate the pregnancy because of Down syndrome. Advocates for Down syndrome state this is similar to eugenics and is often based in fear of the unknown. Further, they argue that many parents given the information of a Down diagnosis are not fully informed on the wide range of the disorder or that there is an adoption waiting list full of people who wish to have a child with Down syndrome.

Advocates for people with Down syndrome also point to various factors, such as special education and parental support groups, that make life easier for parents of children with the disorder. There are also great strides being made in education, housing, and social settings to create "Down-friendly" environments. It is argued that many only view people with Down's in the ways of the past, limiting them to sub-standard possibilities in life and ignoring their very real social needs. In most developed countries, since the early 20th century many people with Down syndrome were housed in "mental subnormality" institutions or colonies and excluded from society. However, in the 21st century there is a moving change among parents, educators and other professionals generally advocate a policy of "inclusion", bringing people with any form of mental or physical disability into general society as much as possible. In many countries, people with Down syndrome are educated in the normal school system and there are increasingly higher quality opportunties to mix "special" education with regular education settings.

Despite this change, the reduced abilities of people with Down syndrome pose a challenge to their parents and families. While living with their parents is preferable to institutionalization for most adults with Down syndrome, they often encounter patronising attitudes and discrimination in the wider community. Social views of persons with Down still rest on the pre-intervention days when babies were immediately isolated and lacked proper social interaction and stimulation. The case is there are wide ranges of ability among persons living with Down and many are capable of living "normal" lives with some degree of assistance just as other disabled persons may. This means people with Down syndrome are able to run their own household, apply for a regular job, get a driver's licence and take care of insurances, etc, by themselves. It is preferable to institutional living, the 1980's and 1990's experiments with group homes were not especially successful, and a number of new models are emerging. In the past few years the independent (supported) living model has found favour with UK governments. With Direct Payments, some people are able to employ their own staff. Individuals can take on their own tenancy,or shared ownership and receive support from a skilled caregiver in organizing their own life, studies, career, and outside interests. For an example of a young woman using Direct Payments for this, see [4]

Notable individuals

Notable people with Down syndrome include:

Down syndrome in fiction

Sources

Further reading

  • Down Syndrome: The Facts. (1997), Selikowitz, M.(2nd ed.). Oxford, UK; New York, NY, USA: Oxford University Press.
  • Down Syndrome: A Promising Future, Together. (1999), Hassold, T. J. and Patterson, D. (Eds.). New York, NY, USA: Wiley Liss.
  • Count us in - Growing up with Down syndrome. (1994) Kingsley, J. and Levitz, M. (1994) San Diego, CA, USA: Harcourt Brace.
  • Medical and Surgical Care for Children with Down Syndrome: A Guide for Parents. (1995) Van Dyke, D. C., Mattheis, P. J., Schoon Eberly, S., and Williams, J. Bethesda, MD, USA: Woodbine House.
  • Adolescents with Down Syndrome: Toward a More Fulfilling Life. (1997) Pueschel, S. M. and Sustrova M. (Eds.) Baltimore, MA, USA: Paul H. Brookes Pub.
  • Living with Down syndrome (2000), Buckley, S. Portsmouth, UK: The Down Syndrome Educational Trust. Also available online: http://www.down-syndrome.info/library/dsii/01/01/
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